TABLE 3.

Genetic approaches for astrocyte targeting

Approach	Concept	Properties	References
Split-Cre	The open reading frame (ORF) of Cre is divided into two parts Each part is expressed by a different promoter	Compatible with all LoxP-flanked alleles Enables cell-type-specific labeling (e.g., with standard reporter alleles), knockout, and analyses (e.g., using RiboTag mice)	Beckervordersandforth et al., 2010; Hirrlinger et al., 2019; Hirrlinger, Scheller, et al., 2009; Jullien et al., 2003; Kim, Kolesnikov, et al., 2021
Split-Cre-ERT2	Tamoxifen inducible version of Split-Cre	Temporal control of Split-Cre mediated recombination	Hirrlinger et al., 2019; Hirrlinger, Requardt, et al., 2009
Split-Cre-Intein	Intein mediated interaction of Cre parts	High-recombination efficiency Works with three promoters (“SpaRCLIN”)	Luan et al., 2020; Salwig et al., 2019; Wang et al., 2012
Combination of different DNA recombinases (e.g., Cre, Dre, Flp)	Each recombinase is driven by a different promoter	Use of full-length recombinases Special reporter alleles necessary Allows cell type targeting by the consecutive activity of promoters or Boolean logic (e.g., promoter 1 active, but not promoter 2)	Jensen & Dymecki, 2014; Liu et al., 2020; Madisen et al., 2015
Light-activated DNA recombinases	Light-induced dimerization of split-DNA recombinases	Precise control of DNA recombination in space and time through light application	Weinberg et al., 2019; Yao et al., 2020
Combination of DNA recombinases and the Tet-system	Two promoters driving Cre and tTA	Combinatorial targeting by Cre and tTA Temporal control by doxycycline application	Ahmadzadeh et al., 2020; Madisen et al., 2015; Rosellό-Díez et al., 2018